Experimental Study Of Clopidogrel’s Impact On MSCs Treatment In Rat Myocardial Infarction

Objective：To investigate the effects of clopidogrel on MSCs ttreatment to myocardialinfarction in rat.Methods：According to the different adherent characteristic of cells, isolate andculture MSCs from the tibia and femur of aged6weeks SD rats. And the passage3th cellswere used to the experiment. In vitro: use flow ctometry to detect the effect of3mg/Lconcentration of clopidogrel on MSCs’ apoptosis, and use transwell to investigate themigration of MSCs under3mg/L concentration of clopidogrel. In vivo: Ligate a branch ofcoronary artery by thoracotomy to finish32myocardial infarctional SD rats weighing200g.They were randomly divided into4groups: GroupⅠwas the blank group, they were gaveplacebo and tranplanted normal saline via the tail vein. GroupⅡwas the clopidogrel group,they were gave placebo and tranplanted normal saline. GroupⅢwas the MSCs group, theywere gave clopidogrel and transplanted MSCs. GroupⅣwas the experimental group, theywere gave clopidogrel and tranplanted MSCs. They were had3mg/kg of placebo orclopidogrel since the2th day after ligated coronary atery, and tranplanted0.5ml of normalsaline or5×106of MSCs in the7th day. In the5th week, we detected the left ventricularejection fraction (LVEF) by color Doppler echocardiography, calculated theBrdU+MSCsand the apoptosis cells in the myocardium using immune enzyme united response.Results:The apoptosis cells of clopidogrel group is low than control group:3.86±0.11%VS13.98±0.31%(P<0.01),there was significantly diference; The migration cells ofclopidogrel group is high than control group:57.90±4.18%VS35.72±3.26%（P<0.01）,there was significantly diference.There was no significantly diference of LVEFbetween GroupⅠand GroupⅡ:39.96±1.58%VS41.71±2.10%(P=0.097>0.05), GroupⅢwere more than GroupⅡ:51.24±1.95%VS41.71±2.10%（P<0.01）, GroupⅣwere more than GroupⅡ:59.73±2.81%VS41.71±2.10%（P<0.01）,GroupⅣwere more than GroupⅢ:59.73±2.81%VS51.24±1.95%（P<0.05）.Brd U positive cells weren’t found inmyocardial slice at GroupⅠand GroupⅡ, while GroupⅣwere more than GroupⅢin everyhigh power field:37.2±3.8VS24.3±1.5（P<0.01）.For the apoptosis cells of myocardium:Group Ⅷ <Group Ⅲ <Group Ⅱ:24.6±0.8VS32.2±2.1VS40.5±1.3,there weresignificantly diference (P<0.01); GrouⅡ<GroupⅠ,But there was no diference betweentwo groups:40.5±1.3VS41.3±1.4,（P=0.21>0.05).Conclusion:1.In vitro Clopidogrel can promote the migration of MSCs and inhibit the apoptosis ofMSCs.2.In vivo Clopidogrel can promote MSCs migrate to the injured myocardium and letmore MSCs play therapeutic roles.3.Clopidogrel can enhance the MSCs effect of in the treatment of acute myocardialinfarction.